Critical Care Obstetrics part 44 pdf

Thrombotic Thrombocytopenic Purpura, Hemolytic–Uremic Syndrome, and HELLP 419 breakdown of antidiuretic hormone (vasopressin) produced by the posterior pituitary gland, and “ resistance to vasopressin ” [164,167] . The small subset of patients with progressive deterio- ration of renal function after delivery may require either tempo- rary or permanent hemodialysis. Fetal morbidity and mortality, once estimated to be anywhere from 5 to 100%, has now decreased to between 9 and 24% [140] . Fetal complications are usually due to prematurity, placental abruption, and intrauterine hypoxia or asphyxia. Some infants (39%) of HELLP syndrome mothers have intrauterine growth restriction (IUGR), and about one - third have thrombocytopenia. Intraventricular hemorrhage occurs in 4% of infants with severe thrombocytopenia [168] . HELLP syndrome itself has been reported to recur in up to 27% of women during subsequent pregnancies [139] and the incidence of any hypertensive disorder of pregnancy (eclampsia, pre - eclampsia, or gestational hypertension) is of the order of 30% in women with previous preterm HELLP syndrome who have another pregnancy [169] . Differential d iagnosis Complications of pregnancy that may be confused with HELLP include TTP, HUS, DIC, sepsis, connective tissue disorders, antiphospholipid antibody syndrome, and acute fatty liver of pregnancy. This latter entity is also seen in the last trimester or postpartum, and presents with thrombocytopenia and right upper quadrant pain; however, the serum levels of AST and ALT increase more modestly (up to about fi vefold) and the PT and APTT are both consistently prolonged. Liver biopsy samples reveal infl ammation and patchy hepatocellular necrosis, and specifi c staining demonstrates fat in the cytoplasm of centrilobular hepatocytes. Because it can cause right upper quadrant pain and nausea, HELLP has been misdiagnosed as viral hepatitis, biliary colic, esophageal refl ux, cholecystitis, and gastric ulcer. Conversely, other conditions misdiagnosed as HELLP syndrome have included cardiomyopathy, dissecting aortic aneurysm, acute cocaine intoxication, essential hypertension with renal disease, and alcoholic liver dysfunction [143] . References 1 Moschcowitz E . Hyaline thrombosis of the terminal arterioles and capillaries: a hitherto undescribed disease . Proc NY Pathol Soc 1924 ; 24 : 21 – 24 . 2 Moschcowitz E . An acute febrile pleiochromic anamia with hyaline thrombosis of the terminal arterioles and capillaries . Arch Intern Med 1925 ; 36 : 89 – 93 . 3 Burns ER , Lou Y , Pathak A . Morphologic diagnosis of thrombotic thrombocytopenic purpura . Am J Hematol 2004 ; 75 : 18 – 21 . 4 James T , Monto R . Pathology of the cardiac conduction system in thrombotic thrombocytopenic purpura . Ann Intern Med 1966 ; 65 : 37 – 43 . CI − 7.13 to − 1.87), mean interval (hours) to delivery (41 ± 15) versus (15 ± 4.5) (p = 0.0068) in favor of women randomised to dexamethasone. There were no signifi cant differences in perinatal mortality or morbidity due to respiratory distress syndrome, need for ventila- tory support, intracerebral hemorrhage, necrotizing enterocolitis and a 5 - min Apgar less than 7. The mean birthweight was signifi - cantly greater in the group allocated to dexamethasone (WMD 247.00; 95% CI 65.41 – 428.59). These authors concluded that based on these fi ve studies there was insuffi cient evidence to determine whether adjunctive steroid use in HELLP syndrome decreases maternal and perinatal mortality, or major maternal and perinatal morbidity. Antepartum plasma exchanges do not arrest or reverse HELLP syndrome; however, peripartum exchanges may minimize hemorrhage and morbidity. Plasma exchanges should probably be employed in women who fail to improve within 72 – 96 hours after delivery. This is a subgroup of about 5% of HELLP patients who are usually either nulliparous or younger than 20 years of age [142,143] . Liver transplantation may eventually be necessary in cases complicated by large destructive hematomas or total hepatic necrosis [163] Although the condition of most HELLP patients stabilizes within 24 – 48 hours following delivery, death occurs in 3 – 5%. Maternal mortality rates as high as 25% were reported prior to 1980, usually because of cerebral hemorrhage, cardiopulmonary arrest, DIC, adult respiratory distress syndrome, or hypoxic isch- emic encephalopathy [139] . Other complications can include infection, abruptio placentae, postpartum hemorrhage, intra - abdominal bleeding, pulmonary edema, retinal detachment, postictal cortical blindness, hypoglycemic coma, and subcapsular liver hematoma with subsequent rupture (mortality about 50%) [140,164] . Patients with the latter complication may complain of right - sided shoulder pain, and may develop shock with ascites and/or pleural effusions. Hepatic hematomas are usually in the anterior superior right lobe. Deep and repeated abdominal palpation, seizures, or vomiting makes rupture and cata- strophic hemorrhage more likely. The safest therapy for hepatic rupture in HELLP syndrome is to pack the liver and abdomen, place a large - bore drain to monitor continued bleeding, close the abdomen and continue supportive therapy with blood and blood product (including activated factor VIIa) transfusion [165,166] . Emergent hepatic artery embolization or ligation, and lobectomy, have been attempted but are associated with signifi - cantly worse outcome than the “ pack and support ” approach. In some cases where total liver shutdown has occurred following massive necrosis, liver transplantation may be necessary [139,143] . Renal complications of HELLP may include transient elevation of serum creatinine, hyponatremia, nephrogenic diabetes insipidus, or acute renal failure. Nephrogenic diabetes insipidus may result in HELLP syndrome from the impaired hepatic metabolism of placental - produced vasopressinase. This inadequately metabolized vasopressinase is postulated to cause excessive Chapter 32 420 23 Venat - Bouvet L , Ly K , Szelag JC , et al. Thrombotic microangiopathy and digital necrosis: two unrecognized toxicities of gemcitabine . Anticancer Drugs 2003 ; 14 : 829 – 832 . 24 George JN . The association of pregnancy with thrombotic thrombocytopenic purpura - hemolytic uremic syndrome . Curr Opin Hematol 2003 ; 10 : 339 – 344 . 25 Sadler JE , Moake JL , Miyata T , George JN . Recent advances in thrombotic thrombocytopenic purpura . Hematology (Am Soc Hematol Educ Program) 2004 ; 407 – 423 . 26 Vesely SK , Li X , McMinn JR , Terrell DR , George JN . Pregnancy outcomes after recovery from thrombotic thrombocytopenic purpura - hemolytic uremic syndrome . Transfusion 2004 ; 44 : 1149 – 1158 . 27 Anacleto FE , Cifra CL , Elises JS . Postpartum hemolytic uremic syndrome in a 17 - year - old Filipina primigravid . Pediatr Nephrol 2003 ; 18 : 1283 – 1285 . 28 Dashe JS , Ramin SM , Cunningham FG . The long - term consequences of thrombotic microangiopathy (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) in pregnancy . Obstet Gynecol 1998 ; 91 : 662 – 668 . 29 Robson JS , Ruckley VA , MacDonald MK . Irreversible post partum renal failure. A new syndrome . QJ Med 1968 ; 37 : 423 . 30 Martinez - Roman S , Gratacos E , Torn é A , et al. Successful pregnancy in a patient with hemolytic - uremic syndrome during the second trimester of pregnancy . J Reprod Med 1996 ; 41 : 211 – 214 . 31 Iannuzzi M , Siconolfi P , d ’ Angelilo A , et al. A post - partum hemolytic - uremic - like - syndrome in a patient with pre - eclampsia: descrip- tion of a clinical case . Transfus Apher Sci 2006 ; 34 : 11 – 14 . 32 Ribeiro FM , Rocha E , Maccariello E , et al. Early gestational hemolytic uremic syndrome: case report and review of literature . Ren Fail 1997 ; 19 : 475 – 479 . 33 Banatvala N , Griffi n PM , Greene KD , et al. The United States National Progressive Hemolytic Uremic Syndrome Study: microbio- logic, serologic, clinical. and epidemiologic fi ndings . J Infect Dis 2001 ; 183 : 1063 – 1070 . 34 Asada Y , Sumiyoshi A , Hayashi T , Suzumiya J , Kaketani K . Immunochemistry of vascular lesions in thrombotic thromocytope- nic purpura, with special reference to factor VIII related antigen . Throm Res 1985 ; 38 : 469 – 479 . 35 Harkness DR , Byrnes JJ , Lian E , Williams W , Hensley GT . Hazard of platelet transfusion in thrombotic thrombocytopenic purpura . JAMA 1981 ; 246 : 1931 – 1933 . 36 Ruggeri ZM . Developing basic and clinical research on von Willebrand factor and von Willebrand disease . Thromb Haemost 2000 ; 84 : 147 – 149 . 37 Arya M , Anvari B , Romo GM , et al. Ultra - large multimers of von Willebrand factor form spontaneous high - strength bonds with the platelet GP Ib - IX complex: studies using optical tweezers . Blood 2002 ; 99 : 3971 – 3977 . 38 Moake JL , Turner NA , Stathopoulos NA , Nolasco LH , Hellums JD . Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress - induced platelet aggregation . J Clin Invest 1986 ; 78 : 1456 – 1461 . 39 Moake JL , Turner NA , Stathopoulos NA , Nolasco L , Hellums JD . Shear - induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin . Blood 1988 ; 71 : 1366 – 1374 . 5 Bell M , Barnhart J , Martin JM . Thrombotic throbocytopenic purpura causing sudden unexpected death – a series of eight patients . J Forens Sci 1990 ; 35 : 601 – 613 . 6 R i d o l fi R , Hutchins G , Bell WR . The heart and cardiac conduction system in thrombotic thrombocytopenic purpura. A clinicopatho- logic study of 17 autopsied patients . Ann Intern Med 1979 ; 91 : 357 – 363 . 7 Moake JL . Thrombotic microangiopathies . N Engl J Med 2002 ; 347 : 589 – 600 . 8 Furlan M , Robles R , Solenthaler M , et al. Defi cient activity of von Willebrand factor - cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura . Blood 1997 ; 89 : 3097 – 3103 . 9 Moake J , Rudy CK , Troll J , et al. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura . N Engl J Med 1982 ; 307 : 1432 – 1435 . 10 Moake J , Chintagumpala M , Turner N , et al. Solvent/detergent - treated plasma suppresses shear - induced platelet aggregation and prevents episodes of thrombotic thrombocytopenic purpura . Blood 1994 ; 84 : 490 – 497 . 11 Bennett C , Davidson CS , Raisch DW , et al. Thrombotic thrombocytopenic purpura associated with ticlopidine: a review of 60 cases . Ann Intern Med 1998 ; 128 : 541 – 544 . 12 Tsai HM , Chandler WL , Sarode R , et al. von Willebrand factor and von Willebrand factor - cleaving metalloprotease activity in Escherichia coli 0157:H7 - associated hemolytic uremic syndrome . Pediatr Res 2001 ; 49 : 653 – 659 . 13 Bennett C , Connors JM , Carwile JM , et al. Thrombotic thrombocytopenic purpura associated with clopidogrel . N Engl J Med 2000 ; 342 : 1773 – 1777 . 14 Atkinson K , Biggs J , Hayes J , et al. Cyclosporin A associated neph- rotoxicity in the fi rst 100 days after allogeneic bone marrow transplantation: three distinct syndromes . Br J Haematol 1983 ; 54 : 59 – 67 . 15 Charba D , Moake J , Harris M , Hester JP . Abnormalities of von Willebrand factor multimers in drug - associated thrombotic microangiopathies . Am J Hematol 1993 ; 42 : 268 – 277 . 16 Gottschall J , et al. Quinine - induced immune thrombocytopenia associated with hemolytic - uremic syndrome: a new clinical entity . Blood 1991 ; 77 : 306 – 310 . 17 Humphreys B , Sharman JP , Henderson JM , et al. Gemcitabine - associated thrombotic microangiopathy . Cancer 2004 ; 100 : 2664 – 2670 . 18 Kojouri K , Vesely SK , George JN . Quinine - associated thrombotic thrombocytopenic - hemolytic uremic syndrome: frequency, clinical features, and long - term outcomes . Ann Intern Med 2001 ; 135 : 1047 – 1051 . 19 Mach - Pascual S , Samii K , Beris P . Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy . Am J Hematol 1996 ; 52 : 310 – 312 . 20 Moake JL , Byrnes JJ . Thrombotic microangiopathies associated with drugs and bone marrow transplantation . Hematol/Oncol Clin North Am 1996 ; 10 : 485 – 497 . 21 Rabadi SJ , Khandekar JD , Miller HJ . Mitomycin - induced hemolytic uremic syndrome: case presentation and review of literature . Cancer Treat Rep 1982 ; 66 : 1244 – 1247 . 22 Singh N , Gayowski T , Marino IR . Hemolytic uremic syndrome in solid - organ transplant recipients . Transplant Int 1996 ; 9 : 68 – 75 . Thrombotic Thrombocytopenic Purpura, Hemolytic–Uremic Syndrome, and HELLP 421 58 Padilla A , Moake JL , Bernardo A , et al. P - selectin anchors newly released ultralarge von Willebrand factor multimers to the endothelial cell surface . Blood 2004 ; 103 : 2150 – 2156 . 59 Bernardo A , Ball C , Nolasco L , Moake JL , Dong JF . Effects of infl am- matory cytokines on the release and cleavage of the endothelial cell - derived ultralarge von Willebrand factor multimers under fl ow . Blood 2004 ; 104 : 100 – 106 . 60 Tao Z , Wang Y , Choi H , et al. Peptides from the C - terminal regions of ADAMTS - 13 specifi cally block cleavage of ultra - large von Willebrand factor multimers on the endothelial surface under fl ow . J Thromb Haemost 2003 ; 1 July, Abstract #OC405 (2003). 61 Majerus EM , Anderson PJ , Sadler JE . Binding of ADAMTS13 to von Willebrand factor . J Biol Chem 2005 ; 280 : 21773 – 21778 . 62 Tao Z , Peng Y , Nolasco L , et al. Recombinant CUB - 1 domain poly- peptide inhibits the cleavage of ULVWF strings by ADAMTS13 under fl ow conditions . Blood 2005 ; 106 : 4139 – 4145 . 63 Nishio K , Anderson PJ , Zheng XL , Sadler JE . Binding of platelet glycoprotein Ibalpha to von Willebrand factor domain A1 stimulates the cleavage of the adjacent domain A2 by ADAMTS13 . Proc Natl Acad Sci USA 2004 ; 101 : 10578 – 10583 . 64 Moake JL , McPherson PD . Abnormalities of von Willebrand factor multimers in thrombotic thrombocytopenic purpura and hemolytic - uremic syndrome . Am J Med 1989 ; 87 : 9N – 15N . 65 Furlan M , Robles R , Solenthaler M , Lammle B . Acquired defi ciency of von Willebrand factor - cleaving protease in a patient with thrombotic thrombocytopenic purpura . Blood 1998 ; 91 : 2839 – 2846 . 66 Bianchi V , Robles R , Alberio L , Furlan M , Lammle B . Von Willebrand factor - cleaving protease (ADAMTS13) in thrombotic thrombocytopenic disorders: a severely defi cient activity is specifi c for thrombotic thrombocytopenic purpura . Blood 2002 ; 100 : 710 – 713 . 67 Bernardo A , Ball C , Nolasco L , et al. Platelets adhered to endothelial cell - bound ultra - large von Willebrand factor strings support leukocyte tethering and rolling under high shear stress . J Thromb Haemost 2005 ; 3 : 562 – 570 . 68 Allford SL , Harrison P , Lawrie AS , et al. Von Willebrand factor - cleaving protease in congenital thrombotic thrombocytopenic purpura . Br J Haematol 2000 ; 111 : 1215 – 1222 . 69 Furlan M , Robles R , Morselli B , Sandoz P , Lammle B . Recovery and half - life of von Willebrand factor - cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura . Thromb Haemost 1999 ; 81 : 8 – 13 . 70 Levy GA , Nichols WC , Lian EC , et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura . Nature 2001 ; 413 : 488 – 494 . 71 Pimanda JE , Maekawa A , Wind T , et al. Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13 . Blood 2004 ; 103 : 627 – 629 . 72 Furlan M , Lammle B . Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and the haemolytic syndrome: the role of von Willebrand factor - cleaving protease . Best Pract Res Clin Haematol 2001 ; 14 : 437 – 454 . 73 Veyradier A , Obert B , Haddad E , et al. Severe defi ciency of the specifi c von Willebrand factor - cleaving protease (ADAMTS 13) activity in a subgroup of children with atypical hemolytic uremic syndrome . J Pediatr 2003 ; 142 : 310 – 317 . 74 Schulman I , Pierce M , Lukens A , Currimbhoy Z . Studies on throm- bopoiesis. I. A factor in normal human plasma required for platelet production; chronic thrombocytopenia due to its defi ciency . Blood 1960 ; 16 : 943 – 957 . 40 Moake JL , Rudy CK , Troll JH , et al. Therapy of chronic relapsing thrombotic thrombocytopenic purpura with prednisone and aza- thioprine . Am J Hematol 1985 ; 20 : 73 – 79 . 41 Furlan M , Robles R , Galbusera M , et al. von Willebrand factor - cleaving protease in thrombotic thrombocytopenic purpura and hemolytic - uremic syndrome . N Engl J Med 1998 ; 339 : 1578 – 1584 . 42 Tsai HM , Lian E . Antibodies of von Willebrand factor cleaving protease in acute thrombotic thrombocytopenic purpura . N Engl J Med 1998 ; 339 : 1585 – 1594 . 43 Furlan M , Robles R , Lammle B . Partial purifi cation and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis . Blood 1996 ; 87 : 4223 – 4234 . 44 Tsai HM . Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its confi rmation and requires calcium ion . Blood 1996 ; 87 : 4235 – 4244 . 45 Tsai HM , Sussman II , Nagel RL . Shear stress enhances the proteolysis of von Willebrand factor in normal plasma . Blood 1994 ; 83 : 2171 – 2179 . 46 Fujikawa K , Suzuki H , McMullen B , Chung D . Purifi cation of von Willebrand factor - cleaving protease and its identifi cation as a new member of the metalloproteinase family . Blood 2001 ; 98 : 1662 – 1666 . 47 Zheng X , Chung D , Takayama TK , et al. Structure of von Willebrand factor - cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura . J Biol Chem 2001 ; 276 : 41059 – 41063 . 48 Bork P , Beckmann G . The CUB domain – a widespread module in developmentally regulated proteins . J Molec Biol 1993 ; 231 : 530 – 545 . 49 Shang D , Zheng XW , Niiya M , Zheng XL . Apical sorting of ADAMTS13 in vascular endothelial cells and Madin - Darby canine kidney cells depends on the CUB domains and their association with lipid rafts . Blood 2006 ; 108 ( 7 ): 2207 – 2215 . 50 Turner N , Nolasco L , Tao Z , Dong JF , Moake J . Human endothelial cells synthesize and release ADAMTS - 13 . J Thromb Haemost 2006 ; 4 : 1396 – 1404 . 51 Niiya M , Uemura M , Zheng XW , et al. Increased ADAMTS - 13 pro- teolytic activity in rat hepatic stellate cells upon activation in vitro and in vivo . J Thromb Haemost 2006 ; 4 : 1063 – 1070 . 52 Uemura M , Tatsumi K , Matsumoto M , et al. Localization of ADAMTS13 to the stellate cells of human liver . Blood 2005 ; 106 : 922 – 924 . 53 Zhou W , Inada M , Lee TP , et al. ADAMTS13 is expressed in hepatic stellate cells . Lab Invest 2005 ; 85 : 780 – 788 . 54 Barbot J , Costa E , Guerra M , et al. Ten years of prophylactic treatment with fresh - frozen plasma in a child with chronic relapsing thrombotic thrombocytopenic purpura as a result of a congenital defi ciency of von Willebrand factor - cleaving protease . Br J Haematol 2001 ; 113 : 649 – 651 . 55 Chung DW , Fujikawa K . Processing of von Willebrand factor by ADAMTS - 13 . Biochemistry 2002 ; 41 : 11065 – 11070 . 56 Dong JF , Moake JL , Bernardo A , et al. ADAMTS - 13 metalloprotease interacts with the endothelial cell - derived ultra - large von Willebrand factor . J Biol Chem 2003 ; 278 : 29633 – 29639 . 57 Dong JF , Moake JL , Nolasco L , et al. ADAMTS - 13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under fl owing conditions . Blood 2002 ; 100 : 4033 – 4039 . Chapter 32 422 purpura in an HIV - positive patient: case report and review of the literature . Am J Hematol 1996 ; 51 : 73 – 78 . 93 Byrnes JJ , Khurana M . Treatment of thrombotic thrombocytopenic purpura with plasma . N Engl J Med 1977 ; 297 : 1386 – 1389 . 94 Frangos JA , Moake JL , Nolasco L , Phillips MD , McIntireL V . Cryosupernatant regulates accumulation of unusually large vWF multimers from endothelial cells . Am J Physiol 1989 ; 256 : H1635 – 44 . 95 Rock GA , Shumak KH , Buskard NA , et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura . N Engl J Med 1991 ; 325 : 393 – 397 . 96 Bell WR , Braine HG , Ness PM , Kickler TS . Improved survival in thrombotic thrombocytopenic purpura - hemolytic - uremic syndrome clinical experience in 108 patients . N Engl J Med 1991 ; 325 : 398 – 403 . 97 Tsai HM . High titers of inhibitors of von Willebrand factor - cleaving metalloproteinase in a fatal case of acute thrombotic thrombocytopenic purpura . Am J Hematol 2000 ; 65 : 251 – 255 . 98 Tsai HM , Li A , Rock G . Inhibitors of von Willebrand factor - cleaving protease in thrombotic thrombocytopenic purpura . Clin Lab 2001 ; 47 : 387 – 392 . 99 Chemnitz J , Draube A , Scheid C , et al. Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab . Am J Hematol 2002 ; 71 : 105 . 100 Gutterman LA , Kloster B , Tsai HM . Rituximab therapy for refractory thrombotic thrombocytopenic purpura . Blood Cells Mol Dis 2002 ; 28 : 385 . 101 Reff M , Carner K , Chambers K , et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20 . Blood 1994 ; 83 : 435 – 445 . 102 Tsai HM , Shulman K . Rituximab induces remission of cerebral ischemia caused by thrombotic thrombocytopenic purpura . Eur J Haematol 2003 ; 70 : 183 – 185 . 103 Zheng X , Pallera AM , Goodnough LT , Sadler JE , Blinder MA . Remission of chronic thrombotic thrombocytopenic purpura after treatment with cyclophosphamide and rituximab . Ann Intern Med 2003 ; 138 : 105 – 108 . 104 Cataland SR , Jin M , Zheng XL , George JN , Wu HM . An evaluation of cyclosporine alone for the treatment of early recurrences of thom- botic thrombocytopenic purpura . J Thromb Haemost 2006 ; 4 ( 5 ): 1162 – 1164 . 105 Crowther MA , Heddle N , Hayward CPM , Warkentin T , Kelton JG . Splenectomy done during hematologic remission to prevent relapse in patients with thrombotic thrombocytopenic purpura . Ann Intern Med 1996 ; 125 : 294 – 296 . 106 Kremer Hovinga JA , Studt JD , Demarmels Biasuitti F , et al. Splenectomy in relapsing and plasma - refractory acquired thrombotic thrombocytopenic purpura . Haematologica 2004 ; 89 : 320 – 324 . 107 Thompson CE , Damon LE , Ries CA , Linker CA . Thrombotic microangiopathies in the 1980s: clinical features, response to treatment, and the impact of the human immunodefi ciency virus epidemic . Blood 1992 ; 80 : 1890 – 1895 . 108 Gordon LI , Kwaan HC , Rossi EC . Deleterious effects of platelet transfusions and recovery thrombocytosis in patients with thrombotic microangiopathy . Semin Hematol 1987 ; 24 : 194 – 201 . 109 Bandarenko N , Brecher ME . United States Thrombotic Thrombocytopenic Purpura Apheresis Study Group (US TTP ASG): 75 Upshaw JD Jr . Congenital defi ciency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia . N Engl J Med 1978 ; 298 : 1350 – 1352 . 76 Vesely SK , George JN , Lammle B , et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura - hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients . Blood 2003 ; 102 : 60 – 68 . 77 Veyradier A , Girma JP . Assays of ADAMTS - 13 activity . Semin Hematol 2004 ; 41 : 41 – 47 . 78 Tsai HM , Rice L , Sarode R , Chow TW , Moake JL . Antibody inhibitors to von Willebrand factor metalloproteinase and increased von Willebrand factor - platelet binding in ticlopidine - associated thrombotic thrombocytopenic purpura . Ann Intern Med 2000 ; 132 : 794 – 799 . 79 Klaus C , Plaimauer B , Studt J , et al. Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura . Blood 2004 ; 103 ( 12 ): 4514 – 4519 . 80 Veyradier A , Obert B , Houllier A , Meyer D , Girma JP . Specifi c von Willebrand factor - cleaving protease in thrombotic microangiopathies: a study of 111 cases . Blood 2001 ; 98 : 1765 – 1762 . 81 Zheng XL , Kaufman RM , Goodnough LT , Sadler JE . Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and non - idiopathic thrombotic thrombocytopenic purpura . Blood 2004 ; 103 ( 11 ): 4043 – 4049 . 82 Oleksowicz L , Bhagwati N , DeLeon - Fernandez M . Defi cient activity of von Willebrand ’ s factor - cleaving protease in patients with dis- seminated malignancies . Cancer Res 1999 ; 59 : 2244 – 2250 . 83 Mannucci PM , Canciani MT , Forza I , et al. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor . Blood 2001 ; 98 : 2730 – 2735 . 84 Neame PD . Immunologic and other factors in thrombotic thrombocytopenic purpura (TTP) . Semin Thromb Hemost 1980 ; 6 : 416 – 429 . 85 Wada H , Kaneko T , Ohiwa M , et al. Plasma cytokine levels in thrombotic thrombocytopenic purpura . Am J Hematol 1992 ; 40 : 167 – 170 . 86 Zauli G , Gugliotta L , Catani L , et al. Increased serum levels of trans- forming growth factor beta - 1 in patients affected by thrombotic thrombocytopenic purpura (TTP): its implications on bone marrow haematopoiesis . Br J Haematol 1993 ; 84 : 381 – 386 . 87 Joseph G , Smith KJ , Hadley TJ , et al. HLA - DR53 protects against thrombotic thrombocytopenic purpura/adult hemolytic uremic syndrome . Am J Hematol 1994 ; 47 : 189 – 193 . 88 Nesher G , Hanna VE , Moore TL , Hersh M , Osborn TG . Thrombotic microangiographic hemolytic anemia in systemic lupus erythema- tosus . Semin Arthritis Rheum 1994 ; 24 : 165 – 172 . 89 Zacharski LR , Lusted D , Glick JL . Thrombotic thrombocytopenic purpura in a previously splenectomized patient . Am J Med 1976 ; 60 : 1061 – 1063 . 90 Leaf AN , Laubenstein LJ , Raphael B , et al. Thrombotic thrombocytopenic purpura associated with human immunodefi ciency virus type 1 (HIV - 1) infection . Ann Intern Med 1988 ; 109 : 194 – 197 . 91 Nair JM , Bellevue R , Bertoni M , Dosik H . Thrombotic thrombocytopenic purpura in patients with the acquired immunodefi ciency syndrome (AIDS) - related complex. A report of two cases . Ann Intern Med 1988 ; 109 : 209 – 212 . 92 Yospur LS , Sun NC , Figueroa P , Niihara Y . Concurrent thrombotic thrombocytopenic purpura and immune thrombocytopenic Thrombotic Thrombocytopenic Purpura, Hemolytic–Uremic Syndrome, and HELLP 423 128 Warwicker P , Goodship TH , Donne RL , et al. Genetic studies into inherited and sporadic hemolytic uremic syndrome . Kidney Int 1998 ; 53 : 836 – 844 . 129 Fremeaux - Bacchi V , Dragon - Durey MA , Blouin J , et al. Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome . J Med Genet 2004 ; 41 : e84 . 130 Byrnes JJ , Moake JL . Thrombotic thrombocytopenic purpura and the hemolytic - uremic syndrome: evolving concepts of pathogenesis and therapy . Clin Haematol 1986 ; 15 : 413 – 442 . 131 Moake JL . Haemolytic - uraemic syndrome: basic science . Lancet 1994 ; 343 : 393 – 397 . 132 Banerjee D , Kupin W , Roth D . Hemolytic uremic syndrome after multivisceral transplantation treated with intravenous immuno- globulin . J Nephrol 2003 ; 16 : 733 – 735 . 133 Gatti S , Arru M , Reggiani P , et al. Successful treatment of hemolytic uremic syndrome after liver - kidney transplantation . J Nephrol 2003 ; 16 : 586 – 590 . 134 Korec S , Schein PS , Smith FP , et al. Treatment of cancer - associated hemolytic - uremic syndrome with staphylococcal protein A immu- noperfusion . J Clin Oncol 1986 ; 4 : 210 – 215 . 135 E, S. Ü ber das Verhalten der Blutpl ä ttchen bei Eklampsie . Zentralbl Gyn ä kol 1922 ; 46 : 391 . 136 Pritchard JA , Weisman RJ , Ratnoff OD , Vosburgh GJ . Intravascular hemolysis, thrombocytopenia and other hematologic abnormalities associated with severe toxemia of pregnancy . N Engl J Med 1954 ; 250 : 89 – 98 . 137 Goodlin RC , Cotton DB , Haesslein HC . Severe edema - proteinuria - hypertension gestosis . Am J Obstet Gynecol 1978 ; 132 : 595 – 598 . 138 Weinstein L . Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy . Am J Obstet Gynecol 1982 ; 142 : 159 – 167 . 139 Rahman TM , Wendon J . Severe hepatic dysfunction in pregnancy . QJM 2002 ; 95 : 343 – 357 . 140 Rath W , Faridi A , Dudenhausen JW . HELLP syndrome . J Perinat Med 2000 ; 28 : 249 – 260 . 141 Sibai BM , Ramadan MK , Usta I , et al. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) . Am J Obstet Gynecol 1993 ; 169 : 1000 – 1006 . 142 Magann EF , Bass D , Chauhan SP , et al. Antepartum corticosteroids: disease stabilization in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) . Am J Obstet Gynecol 1994 ; 171 : 1148 – 1153 . 143 Magann EF , Martin JNJ . Twelve steps to optimal management of HELLP syndrome . Clin Obstet Gynecol 1999 ; 42 : 532 – 550 . 144 Zusterzeel PL , Visser W , Blom HJ , et al. Methylenetetrahydrofolate reductase polymorphisms in pre - eclampsia and the HELLP syndrome . Hypertens Pregn 2000 ; 19 : 299 – 307 . 145 Benedetto C , Marozio L , Salton L , et al. Factor V Leiden and factor II G20210A in preeclampsia and HELLP syndrome . Acta Obstet Gynecol Scand 2002 ; 81 : 1095 – 1100 . 146 Bozzo M , Carpani G , Leo L , et al. HELLP syndrome and factor V Leiden . Eur J Obstet Gynecol Reprod Biol 2001 ; 95 : 55 – 58 . 147 Krauss T , Augustin HG , Osmers R , et al. Activated protein C resistance and factor V Leiden in patients with hemolysis, elevated liver enzymes, low platelets syndrome . Obstet Gynecol 1998 ; 92 : 457 – 460 . 148 Marchand A , Galen RS , van Lente F . The predictive value of serum haptoglobin in hemolytic disease . JAMA 1980 ; 243 : 1909 – 1911 . multicenter survey and retrospective analysis of current effi cacy of therapeutic plasma exchange . J Clin Apher 1998 ; 13 : 133 – 141 . 110 Egan JA , Hay SN , Brecher ME . Frequency and signifi cance of schis- tocytes in TTP/HUS patients at the discontinuation of plasma exchange therapy . J Clin Apher 2004 ; 19 : 165 – 167 . 111 Gutterman LA , Stevenson TD . Treatment of thrombotic thrombocytopenic purpura with vincristine . JAMA 1982 ; 247 : 1433 – 1436 . 112 Rosove MH , Ho WG , Goldfi nger D . Ineffectiveness of aspirin and dipyridamole in the treatment of thrombotic thrombocytopenic purpura . Ann Intern Med 1982 ; 96 : 27 – 33 . 113 Plaimauer B , Zimmerman K , Volkel D , et al. Cloning, expression, and functional characterization of the von Willebrand factor - cleaving protease (ADAMTS13) . Blood 2002 ; 100 : 3626 – 3632 . 114 Howard MA , Williams LA , Terrell DR , et al. Complications of plasma exchange in patients treated for clinically suspected thrombotic thrombocytopenic purpura - hemolytic uremic syndrome . Transfusion 2006 ; 46 ( 1 ): 154 – 156 . 115 Reutter JC , Sanders KF , Brecher ME , Jones HG , Bandarenko N . Incidence of allergic reactions with fresh frozen plasma or cryo - supernatant plasma in the treatment of thrombotic thrombocytopenic purpura . J Clin Apher 2001 ; 16 : 134 – 138 . 116 Mori Y , Wada H , Gabazza EC , et al. Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF - cleaving protease activity . Transfusion 2002 ; 42 : 572 – 580 . 117 Raife T , Atkinson B , Montgomery R , Vesely S , Friedman K . Severe defi ciency of VWF - cleaving protease (ADAMTS13) activity defi nes a distinct population of thrombotic microangiopathy patients . Transfusion 2004 ; 44 : 146 – 150 . 118 Elliott MA , Nichols WL Jr , Plumhoff EA , et al. Posttransplantation thrombotic thrombocytopenic purpura: a single - center experience and a contemporary review . Mayo Clin Proc 2003 ; 78 : 421 – 430 . 119 van der Plas RM , Schiphorst ME , Huizinga EG , et al. von Willebrand factor proteolysis is defi cient in classic, but not in bone marrow transplantation - associated thrombotic thrombocytopenic purpura . Blood 1999 ; 93 : 3798 – 3802 . 120 Volcy J , Nzerue CM , Oderinde A , Hewan - Iowe K . Cocaine - induced acute renal failure, hemolysis, and thrombocytopenia mimicking thrombotic thrombocytopenic purpura . Am J Kidney Dis 2000 ; 35 : E3 . 121 Gasser C , Gautier E , Steck A , Siebenmann RE , Oechslin R . [Hemolytic - uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia.] . Schweiz Med Wochenschr 1955 ; 85 : 905 – 909 . 122 Moake JL . Haemolytic - uremic syndrome: basic science . Lancet 1994 ; 343 : 393 – 397 . 123 Kaplan BS , Proesmans W . The hemolytic uremic syndrome of child- hood and its variants . Semin Hematol 1987 ; 24 : 148 – 160 . 124. Karmali MA . Infection by Shiga toxin - producing Escherichia coli: an overview . Mol Biotechnol 2004 ; 26 : 117 – 122 . 125 Karmali MA , Petric M , Lim C , et al. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin - producing Escherichia coli . J Infect Dis 1985 ; 151 : 775 – 782 . 126 Nolasco L , Turner NA , Bernardo A , et al. Hemolytic uremic syndrome - associated Shiga toxins promote endothelial - cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers . Blood 2005 ; 106 : 4199 – 4209 . 127 Bonnardeaux A , Pichette V . Complement dysregulation in haemolytic uraemic syndrome . Lancet 2003 ; 362 : 1514 – 1515 . Chapter 32 424 149 Wilke G , Rath W , Schutz E , Armstrong VW , Kuhn W . Haptoglobin as a sensitive marker of hemolysis in HELLP - syndrome . Int J Gynaecol Obstet 1992 ; 39 : 29 – 34 . 150 Shukla PK , Sharma D , Mandal RK . Serum lactate dehydrogenase in detecting liver damage associated with pre - eclampsia . Br J Obstet Gynaecol 1978 ; 85 : 40 – 42 . 151 Thiagarajah S , Bourgeois FJ , Harbert G , Caudle MR . Thrombocytopenia in preeclampsia: associated abnormalities and management principles . Am J Obstet Gynecol 1984 ; 150 : 1 – 7 . 152 Barton JR , Riely CA , Adamec TA , et al. Hepatic histopathologic condition does not correlate with laboratory abnormalities in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) . Am J Obstet Gynecol 1992 ; 167 : 1538 – 1543 . 153 de Boer K , Buller HR , ten Cate JW , Treffers PE . Coagulation studies in the syndrome of haemolysis, elevated liver enzymes and low platelets . Br J Obstet Gynaecol 1991 ; 98 : 42 – 47 . 154 Thomas EA , Copplestone JA , Dubbins PA , Friend JR . The radiolo- gist cries “ HELLP ” ! . Br J Radiol 1991 ; 64 : 964 – 966 . 155 Zhou Y , McMaster M , Woo K , et al. Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome . Am J Pathol 2002 ; 160 : 1405 – 1423 . 156 Knerr I , Beinder E , Rascher W . Syncytin, a novel human endogenous retroviral gene in human placenta: evidence for its dysregulation in preeclampsia and HELLP syndrome . Am J Obstet Gynecol 2002 ; 186 : 210 – 213 . 157 Levine RJ , Maynard SE , Qian C , et al. Circulating angiogenic factors and the risk of preeclampsia . N Engl J Med 2004 ; 350 : 672 – 683 . 158 Lattuada A , Rossi E , Calzarossa C , Candolfi R , Mannucci PM . Mild to moderate reduction of a von Willebrand factor cleaving protease (ADAMTS - 13) in pregnant women with HELLP microangiopathic syndrome . Haematologica 2003 ; 88 : 1029 – 1034 . 159 Thorp JMJ , White G , Moake JL , Bowes W . von Willebrand factor multimeric levels and patterns in patients with severe preeclampsia . Obstet Gynecol 1990 ; 75 : 163 – 167 . 160 Schlenzig C , Maurer S , Goppelt M , Ulm K , Kolben M . Postpartum curettage in patients with HELLP - syndrome does not result in accelerated recovery . Eur J Obstet Gynecol Reprod Biol 2000 ; 91 : 25 – 28 . 161 Fonseca JE , Mendez F , Catano C , Arias F . Dexamethasone treatment does not improve the outcome of women with HELLP syndrome: a double - blind, placebo - controlled, randomized clinical trial . Am J Obstet Gynecol 2005 ; 193 ( 5 ): 1591 – 1598 . 162 Matchaba P , Moodley J . Corticosteroids for HELLP syndrome in pregnancy . Cochrane Database of Systematic Reviews 2004 , Issue 1 . Art. No.: CD002076. 163 Erhard J , Lange R , Niebel W , et al. Acute liver necrosis in the HELLP syndrome: successful outcome after orthotopic liver transplantation. A case report . Transpl Int 1993 ; 6 : 179 – 181 . 164 Reubinoff BE , Schenker JG . HELLP syndrome – a syndrome of hemolysis, elevated liver enzymes and low platelet count – complicating preeclampsia - eclampsia . Int J Gynaecol Obstet 1991 ; 36 : 95 – 102 . 165 Smith LG Jr , Moise KJ Jr , Dildy GA 3rd , Carpenter RJ Jr . Spontaneous rupture of liver during pregnancy: current therapy . Obstet Gynecol 1991 ; 77 ( 2 ): 171 – 175 . 166 Merchant SH , Mathew P , Vanderjagt TJ , Howdieshell TR , Crookston KP . Recombinant factor VIIa in management of spontaneous subcapsular liver hematoma associated with pregnancy . Obstet Gynecol 2004 ; 103 ( 5 Pt 2 ): 1055 – 1058 . 167 Yamanaka Y , Takeuchi K , Konda E , et al. Transient postpartum diabetes insipidus in twin pregnancy associated with HELLP syndrome . J Perinat Med 2002 ; 30 : 273 – 275 . 168 Harms K , Rath W , Herting E , Kuhn W . Maternal hemolysis, elevated liver enzymes, low platelet count, and neonatal outcome . Am J Perinatol 1995 ; 12 : 1 – 6 . 169 van Pampus MG , Wolf H , Mayruhu G , Treffers PE , Bleker OP . Long - term follow - up in patients with a history of (H)ELLP syndrome . Hypertens Pregn 2001 ; 20 : 15 – 23 . 425 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 33 Endocrine Emergencies Carey Winkler & Fred Coleman Legacy Health Systems, Maternal - Fetal Medicine, Portland, OR, USA Introduction Disorders of the endocrine system are not uncommon in women of childbearing age and therefore, are not uncommon during pregnancy. Signifi cant disturbances of many of the endocrine organs can result in dramatic alterations in maternal physiology which in turn, may affect the maternal – placental – fetal unit. Early recognition and rapid correction of these abnormalities will result in improved maternal and fetal outcomes. This chapter reviews the management of the more common (and severe) endocrine emergencies seen in obstetrics: diabetic ketoacidosis, thyroid disorders, pheochromocytoma, adrenal crisis, and altered parathy- roid states. Diabetic k etoacidosis In recent years, diabetes has accounted for approximately 3 – 5% of all maternal mortality. Of these, 15% were secondary to diabetic ketoacidosis (DKA) [1] . Because of improvements in care provided to critically ill patients, along with prompt recognition and treatment, the risk of maternal death from an episode of DKA is now 1% or less [2] . Unfortunately, the fetal death rate has not fallen to that level. Despite aggressive treatment of the mother and improvements in perinatal and neonatal care, studies suggest a 10 – 25% fetal loss rate for a single episode of DKA [3,4] . Factors that predispose pregnant patients to DKA include accelerated starvation, dehydration, decreased caloric intake secondary to pregnancy - related nausea, decreased buffering capacity (compensated respiratory alkalosis), stress, and increased insulin antagonists such as human placental lactogen, prolactin, and cortisol [5] . The most common precipitating events in DKA are infection related (viral or bacterial 30%) and inadequate insulin treatment usually from patient non - compliance (30%). Other less common reasons include insulin pump failure and medica- tions (glucocorticoids with/without β - adrenergic agents) for preterm labor [6 – 8] . In one series, 7 of 11 patients decreased their insulin dosage because of decreased food intake and lower glucose levels [9] . In addition, Montoro et al. [4] noted that 6 of 20 patients who presented with DKA were newly diagnosed with diabetes. In a retrospective study by Cullen and associates [9] , 11 pregnant patients presented in diabetic ketoacidosis over a 10 - year period. Of these 11 patients, four had an initial blood glucose < 200 mg/dL. The precipitating event for ketoacidosis in these four cases was maternal nausea and vomiting due to an underlying gastrointestinal disorder such as hyperemesis gravidarum or a viral gastroenteritis. In response to the persistent nausea and vomiting, these patients reduced not only their caloric intake but also their insulin dose. Thus, it is important to remember that when an insulin - dependent diabetic presents with a history of persistent nausea and vomiting, a blood glucose < 200 mg/dL does not necessarily eliminate the potential for ketoacidosis. Under these circumstances, an evaluation for the potential of diabetic ketoacidosis should be undertaken. The underlying cause of DKA is an absolute, or more commonly during pregnancy, a relative defi ciency in circulating insulin levels in relationship to an excess of insulin counter - regulatory hormones, specifi cally catecholamines, glucagon, cortisol, and growth hormone. The sequence of events has been reviewed by Kitabchi et al. [8] . The levels of catecholamines (700 – 800%), glucagon (400 – 500%), cortisol (400 – 500%), and growth hormone (200 – 300%) are all increased during DKA when compared to baseline levels. The net result is an increase in glucose levels and hyperglycemia. Glucagon increases production of hepatic ketone bodies from fatty acids. Because insulin is also needed for the effective degradation of ketone bodies, the excessive degree of ketonemia is due to both overproduction as well as continued undermetabolization. The main ketone bodies are β - hydroxybutyric acid, acetic acid, and acetone. These are moderately strong acids and when released Chapter 33 426 conversion to acetoacetate. Paradoxically, the nitroprusside reac- tion may worsen as the condition of the patient improves. However, there should be an improvement in the patient ’ s pH, a decrease in the anion gap, and an overall improvement in the patient ’ s clinical condition. In order to optimize maternal/fetal outcome, the diagnosis needs to be made quickly with immediate initiation of treatment [4] . Therapy should consist of rapidly correcting the volume defi cits, initiation of insulin, treatment of infection if present, and careful monitoring to aid in correction of the metabolic and electrolyte abnormalities. A transurethral catheter should be placed and urine sent for culture and sensitivity. The initial intravenous solution replacement consists of isotonic saline (0.9% NaCl) solution at 1000mL/h for at least 2 hours. Using a hypo- tonic intravenous solution such as half - normal saline (0.45% NaCl) solution can lead to rapid decline in serum osmolarity. If this occurs too quickly for intracellular equilibrium to take place, rarely, cellular swelling can occur, leading to cerebral edema [10] . After 2 L of an isotonic solution over 2 hours, the solution should be changed to one more similar to electrolyte losses during osmotic diuresis (0.45% NaCl) given at 250 mL/h, until serum glucose is between 200 and 250 mg/dL. Continuing the use of an isotonic saline solution can result in excessive chloride and metabolic acidosis during the resolution phase. Once glucose levels reach 250 mg/dL, intravenous fl uids should be changed to 0.45% NaCl with 5% dextrose to prevent an excessively rapid drop in serum glucose. Approximately 75% of the total fl uid replacement should occur during the fi rst 24 hours and the remaining 25% over the next 24 – 48 hours. Unless there are signs of severe dehydration and cardiovascular collapse, a good estimate of the total fl uid loss is 100 mL/kg actual body weight. Since DKA is precipitated by an absolute or relative defi ciency in insulin, it is critical that insulin therapy is started in order to correct the many metabolic abnormalities that have occurred. Treatment should be an initial intravenous bolus followed by continuous infusion. Intramuscular or subcutaneous therapy should be avoided as decreased perfusion may result in inadequate absorption [8] . The initial bolus should be in the neighbor- hood of 10 units of regular insulin (0.1 units/kg) followed by a continuous infusion of 0.1 units/kg/h. Serum glucose levels should be determined every hour. The decrease in serum glucose levels should be gradual to prevent excessive movement of water into the cells from a rapid drop in serum osmolarity. A reasonable target is a decrease of 50 – 75 mg/dL every hour. If serum glucose levels fail to decrease by at least 50 mg/dL in the fi rst 2 hours, the rate of insulin infusion should be doubled [8] . The insulin infusion should be maintained until most of the metabolic abnormalities have corrected and the patient is feeling well enough to eat. At that time, subcutaneous insulin can be initiated and the insulin infusion discontinued. A thorough search for and treatment of the precipitating event and continuation of insulin is necessary to limit recurrence. In DKA, there is a signifi cant loss in total body sodium and potassium. The total body loss of potassium can approach over into the maternal circulation, exceed the maternal buffering capacity of the serum bicarbonate, resulting in the metabolic acidosis component of DKA. As hydrogen ions move into the intracellular space from the extracellular compartment, potassium ions shift in the opposite direction. As a result, there is a depletion of intracellular potassium stores that may be greater than indicated by plasma levels. Maternal respiratory changes to excrete carbon dioxide include an increase in the rate and depth of inspirations, also known as Kussmaul respirations. This results in a compensatory respiratory alkalosis. As the degree of hyperglycemia and ketonemia increases, there is a rise in serum osmolarity. In addition, the hyperglycemia and ketonuria result in a profound osmotic diuresis and severe dehydration. Hypovolemia and hypotension soon follow, resulting in decreased peripheral perfusion, increased production of lactic acid, and a further decrease in serum pH. This sequence of events sets up a vicious cycle of worsening dehydration, increasing serum osmolarity, increasing release of insulin counter - regulatory hormones from stress and cellular dysfunction, and worsening acidosis. The loss of free water from osmotic diuresis can be extensive: up to 150 mL/kg body weight. In a typical pregnant patient, this equates to 7 – 10 L of free water. Along with the loss of urinary water, there is the depletion of many electrolytes, specifi cally sodium, potassium, and phosphorus. The hypovolemia and hypotension may result in emesis, which can exacerbate dehydration and electrolyte losses. Finally, the increased respiratory rate can cause additional water loss and dehydration. Usually, the diagnosis is quite obvious from a clinical perspec- tive. The patient will present with feelings of malaise, emesis, weakness/lethargy, polyuria, polydipsia, tachypnea, and signs of dehydration (decreased skin turgor, dry mucous membranes, tachycardia, hypotension). The patient may complain of fever, suggesting infection as a precipitating event. Because of the decreased peripheral perfusion and resultant ischemia, patients may have abdominal pain of such severity that it may mimic an intra - abdominal process such as appendicitis. Acetone is highly volatile and is excreted in the patient ’ s breath, producing a classic fruity smell. Laboratory evaluation should include serum electrolytes, osmolality, creatinine, blood urea nitrogen, urine leukocyte ester- ase, and arterial blood gases. Classically, the serum glucose will be elevated to 300 mg/dL or more. An arterial blood gas will confi rm an acidotic pH ( < 7.30) along with a decreased serum bicarbonate level. The anion gap will be increased ( > 12) suggesting the presence of non - volatile acids. Finally, the serum will test strongly for acetone (1 : 2 dilution or greater). The predominant ketone produced in DKA is β - hydroxybutyric acid. A commonly used test for evaluating the presence of ketones is the nitroprusside reactions. Neither β - hydroxybutyric acid nor acetone reacts as strongly with nitroprusside as acetoacetate. Therefore, the severity of the ketonemia may be severely underestimated by this test. If possible, direct measurement of plasma β - hydroxybutyric acid should be performed. As insulin therapy is begun, there is a preferential fall in the level of β - hydroxybutyric acid and increased Endocrine Emergencies 427 in fact, is becoming discouraged. Sodium bicarbonate treatment has failed to show a difference in outcome in DKA with a pH in the range of 6.8 – 7.1 [8,11] . However, due to the paucity of patients with a pH 6.9 – 7.0, it is diffi cult to state whether bicarbonate replacement was helpful in this subset of cases. Therefore, if the patient has a pH less than 7.0 or the serum bicarbonate levels is < 5 mEq/L, administration of one ampule (44 mEq) is prudent. Otherwise, the treatment of choice is correction of the underlying problem with hydration, insulin, and potassium. Rapid administration of sodium bicarbonate has the potential to cause paradoxical central nervous system acidosis, as the blood – brain barrier is freely permeable to carbon dioxide but not bicarbonate. For overall management options, see Figure 33.1 . One fi nal point is evaluation and care of the fetus. Fetal distress may occur due to several mechanisms. Uterine blood fl ow may decrease due to catecholamine - induced vasoconstriction or dehydration. Secondly, fetal β - hydroxybutyric acid and glucose concentrations parallel maternal levels [12] and fetal hyperglycemia may in itself lead to an osmotic diuresis, fetal intravascular volume depletion, and decreased placental perfusion. Finally, a leftward shift of the oxygen dissociation curve with a decreased 2,3 - diphosphoglycerate increases hemoglobin affi nity for oxygen and reduces tissue oxygen delivery. In any case, uterine blood 300 mEq. As the acidosis is corrected, potassium ions shift intra- cellularly. The intracellular movement of potassium is accelerated in the presence of insulin and can lead to a precipitous decrease in the serum potassium level. As the patient ’ s volume status improves, potassium levels must be followed closely and imme- diately corrected when low. It is important to replace potassium slowly and not cause hyperkalemia. Serum potassium levels should be determined every 2 – 4 hours depending on the levels. Two ways to replace potassium are as follows. 1 Add KCl (40 mEq/L) to each liter of replacement fl uids and run at the usual 150 – 250 mL/h. This will give approximately 5 – 10 mEq/h replacement. 2 Intermittent intravenous infusion boluses: in an additional intravenous port, give 10 mEq/h infusion for 4 – 6 hours, check the serum potassium level, and continue the “ piggyback ” infusion as necessary. Because of concerns for toxicity/cardiac arrhythmias, potassium supplements should not be given more quickly than 20 mEq/h. After the patient is stable and eating a regular diet, oral supplementation can be given for 1 – 2 days to completely replen- ish the total body stores of potassium. The use of intravenous bicarbonate to increase pH and improve organ function has become a minority view and for most patients, MANAGEMENT OF PREGNANT PATIENT WITH DKA** Lateral uterine displacement Oxygen therapy Fetal monitoring if viable Transurethral catheter Maintain urine output at > 50 cc/hr Initial IV fluids: NS at 1 lit/hr X 2 hrs After 2 hrs, then convert to 1/2 NS at 250 cc/hr When serum glucose is 200–250 mg/dl, convert to D5 1/2 NS at 250 cc/hr Continue for 24–48 hours Detailed H&P Oxygen saturation monitoring Rule out infection Urine culture Chest x-ray if indicated Amniocentesis if contractions 10–15 unit IV bolus 0.1 units/kg/hr IV to decrease serum glucose by 50–75 mg/dl/hr If serum glucose does not decrease by 50 mg/dl in first hour then double the rate of the infusion When serum glucose is 200 mg/dl, decrease rate to 0.05 units/kg/hr Maintain serum glucose in 150-200 mg/dl range Based on initial postassium level and normal renal output (> 50 cc/hr) If serum K+ is < 3.3 mEq/L, then hold insulin infusion If serum K+ is > 5.3 mEq/L, repeat every 2 hrs until < 5.3 mEq/L If serum K+ is 3.3 – 5.3 mEq/L, add 20–30 mEq to each liter of replacement fluids to maintain K + in the range of 4–5 mEq/L No NaHCO3 if maternal pH > 7.0 If pH is < 7.0, then 100 mmol NaHCO3 in 500 cc 1/2 NS with 20 mEq of K + over 2 hours Repeat every 2 hours until pH > 7.0 Once patient is stable and tolerating oral intake, convert to usual subcutaneous dose of insulin ** for patients that meet the criteria for DKA with hyperglycemia and evidence of significant ketosis Maternal Assessment Insulin Therapy (regular) Potassium Management Fetal Assessment Volume Replacement Bicarbonate Management Figure 33.1 Management of pregnant patient with DKA. Chapter 33 428 147 µ g/day, or an increase of 45%. Second, in the acute setting of thyroid storm, it is logical to use propylthiouracil instead of methimazole as the former inhibits peripheral conversion of T4 to T3, while the latter does not. Finally, clinical symptomatic improvement in patients with acute hyperthyroidism treated with propylthiouracil (measured in days) precedes normalization of thyroid function tests (which may take 6 – 8 weeks). Hyperthyroidism Hyperthyroidism during pregnancy is rare, complicating less than 0.2% of all births [27,29] . Early treatment and normalization of maternal thyroid function is important because poor metabolic control increases the risk of preterm delivery, fetal wastage, and thyroid crisis [27,28] . By far the most common cause of thyrotoxicosis during pregnancy is Graves ’ disease, accounting for greater than 90% of cases [30,31] . Less common causes are listed in Table 33.1 and include thyroid adenomas, thyroiditis, or secondary hCG - dependent disorders. Graves ’ disease is an autoimmune disorder where maternal antibodies (thyrotropin receptor antibodies or TRAb) attach to the thyroid gland and stimulate the production of thyroid hormone, similar to TSH. Prior to the use of thionamides, it was recognized that some 25% of patients undergo long - term remission without therapy [32] . During pregnancy, the course is vari- able. As in other autoimmune disorders, some patients appear to improve during pregnancy and relapse postpartum. Amino et al. [33] noted in women with Graves ’ disease near remission at the fl ow may be reduced in poorly controlled diabetics [13] . A signifi cant reduction in the maternal pH thus will result in a cor- responding fall in fetal pH. This will often be refl ected in abnormal fetal heart rate tracings. Unless there are other overriding reasons for prompt delivery, it is usually prudent to correct the underlying DKA, as the abnormal fetal heart rate tracings and Doppler studies seen in maternal ketoacidosis improve with diabetic control [14,15] . In the majority of cases, improving the maternal condition allows for prolongation of the pregnancy. Thyroid d ysfunction Multiple changes occur in the maternal and fetal thyroid gland during pregnancy. These physiologic changes have been exten- sively detailed [16,17] . A brief review of changes that affect the interpretation of thyroid tests or thyroid hormone metabolism in relationship to clinical management follows. Changes in thyroid hormone levels during pregnancy occur both in the maternal circulation and in the developing fetus. Thyroid - binding globulin (TBG) levels increase during pregnancy secondary to an estrogen - stimulated increase in synthesis and a decrease in clearance that is associated with altered sialylation of TBG [18] . Because of the increase in TBG, there is also an increase in the total thyroxine (T4) blood levels in the maternal circulation. Maternal free T4 and free triiodothyronine (T3) blood levels remain within the range of normal values but are minimally decreased in the second and third trimester [16,19] . Sensitive thyroid - stimulating hormone (TSH) and free T4 assays have replaced the free T4 index and have improved the diagnosis of thyroid disorders during pregnancy. The newer TSH assays are extremely sensitive for determining early hypothyroidism. The current upper limits of the normal range is 4.5 mU/L but because 95% of the normal population have a TSH < 2.5 mU/L, there is growing support to decrease the normal values [20] . However, currently, there is no compelling evidence that early treatment of these “ borderline hypothyroid ” pregnant patients compared to close follow - up improves long - term outcomes [21] . In the non - pregnant patient, there are accumulating data suggesting treatment of subclinical hypothyroidism decreases morbidity, especially cardiovascular disease [22 – 24] . One exception to the interpretation of free T4 and TSH during pregnancy is the increase in maternal free T4 and decrease in TSH at 8 – 12 weeks of gestation when human chorionic gondatotropin (hCG) levels peak [17] . This is thought, in part, to refl ect the weak thyrotropic activity of hCG. Thus, a mild elevation of free T4 and suppressed TSH level in the fi rst trimester, in the absence of clinical signs of thyrotoxicosis, is more likely to refl ect a physiologic adjustment and does not suggest hyperthyroidism. The clinical consequences of T4 metabolism are threefold. The fi rst is that thyroid replacement in the hypothyroid patient is usually initiated at 100 µ g/day [25,26] and often increases during pregnancy. Mandel et al. [25] found that to normalize TSH levels in pregnant women, the mean T4 dose increased from 102 to Table 33.1 Causes of hyperthyroidism. Autoimmune Graves ’ disease Hashimoto ’ s disease Autonomous Toxic multinodular goiter Solitary toxic adenoma Thyroiditis (transient) Postpartum thyroiditis Subacute thyroiditis Painless thyroiditis Drug induced Iodide - induced (Jod – Basedow) Radiocontrast agents Thyroxine (factitous or dietary supplements containing thyroid hormones) Secondary TSH - secreting tumor hCG dependent (hyperemesis gravidarum, hydatidiform mole) Thyroid hormone resistance Ectopic struma ovarii Metastatic follicular carcinoma . 425 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 33 Endocrine Emergencies Carey Winkler. thrombocytopenic purpura - hemolytic uremic syndrome . Transfusion 2004 ; 44 : 1149 – 1158 . 27 Anacleto FE , Cifra CL , Elises JS . Postpartum hemolytic uremic syndrome in a 17 - year - old Filipina. – 4234 . 44 Tsai HM . Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its confi rmation and requires calcium ion . Blood 1996 ; 87 : 4235 – 4 244 . 45 Tsai

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